Peripheral nerve injury (PNI) is a common and incurable disease in the clinic, but the effects of available treatments are still not satisfactory. Therefore, it is necessary to explore new treatment methods. To explore the effect and mechanism of melatonin in peripheral nerve regeneration, we administered melatonin to mice with PNI by intraperitoneal injection. We applied microarray analysis to detect differentially expressed genes of mice with sciatic nerve injury after melatonin application. Then, we conducted gene ontology and protein–protein interactions to screen out the key genes related to peripheral nerve regeneration. Cell biology and molecular biology experiments were performed in Schwann cells in vitro to verify the key genes identified by microarray analysis. Our results showed that a total of 598 differentially expressed genes were detected after melatonin subcutaneously injecting into mice with sciatic nerve injury. Bioinformatics analysis showed that Shh may be the key gene for the promotion of peripheral nerve regeneration by melatonin. In vitro, the proliferation and migration abilities of schwann cells in the melatonin group were significantly higher than those of Schwann cells in the control group; while after treating with both melatonin and luzindole (a Shh signalling pathway inhibitor), the proliferation and migration abilities of Schwann cells decreased compared with the melatonin group. Our study suggests that melatonin might improve the proliferation and migration of Schwann cells via the Shh signalling pathway after PNI, thus promoting peripheral nerve regeneration. Our study provides a new approach and target for the clinical treatment of PNI.

中文翻译：

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褪黑素通过周围神经损伤后的shh信号通路促进雪旺细胞增殖和迁移

周围神经损伤（PNI）在临床上是一种常见且无法治愈的疾病，但是可用治疗的效果仍不令人满意。因此，有必要探索新的治疗方法。为了探讨褪黑激素在周围神经再生中的作用和机制，我们通过腹膜内注射将褪黑激素给予患有PNI的小鼠。我们应用微阵列分析来检测褪黑激素应用后的坐骨神经损伤小鼠的差异表达基因。然后，我们进行了基因本体论和蛋白质间相互作用，以筛选出与周围神经再生相关的关键基因。在体外对Schwann细胞进行了细胞生物学和分子生物学实验，以验证通过微阵列分析鉴定的关键基因。我们的结果表明，将褪黑激素皮下注射到坐骨神经损伤小鼠中后，共检测到598个差异表达基因。生物信息学分析表明，Shh可能是褪黑激素促进周围神经再生的关键基因。在体外，褪黑素组的雪旺细胞的增殖和迁移能力显着高于对照组的雪旺细胞。与褪黑素组相比，施褪黑素和Luzindole（Shh信号通路抑制剂）共同治疗后，雪旺氏细胞的增殖和迁移能力下降。我们的研究表明，褪黑激素可能通过PNI后的Shh信号通路改善雪旺细胞的增殖和迁移，从而促进周围神经的再生。